A multidisciplinary effort is underway to design and synthesize (a) an antineoplastic agent effective against slow growing tumors, and (b) a radiosensitizing agent to selectively sensitize hypoxic tumor cells towards treatment with radiation. Triphenylphosphinegold complex of thymidine has been shown in our preliminary experiments to possess potent antineoplastic activity against P388 leukemia and B16 melanoma. Drug distribution studies of the gold complex will be carried out to determine the localization of gold in various tissues. Development of radiosensitizers has been undertaken to overcome the problem of radioresistance of hypoxic cells present in tumors toward ionizing radiation. An extensive structure activity relationship study is being carried out for nitroimidazole analogs in an attempt to reduce the CNS toxicity and increase therapeutic efficacy. To this end, a variety of 2-nitroimidazole nucleosides will be synthesized and tested for radiosensitization by in vitro and in vivo techniques. Pharmacokinetic experiments will be conducted for a new radiosensitizer, 1-(2',3'-didehydro-2',3'-dideoxy-alpha-D-erythro-hexopyranosyl)-2-nitro-imidazol e (RA263).